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Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Note that this randomized trial evaluating subcutaneous belimumab for the treatment of systemic lupus erythematosus found the agent to be superior to placebo in terms of reducing future flares.

The effects appear to be more profound in those with serologically active disease, though effects were still seen among those without hypocomplementemia.

LONDON -- Patients with systemic lupus erythematosus (SLE) with serologically active disease had a significantly decreased likelihood of experiencing a severe flare if treated with subcutaneous belimumab (Benlysta), according to a post-hoc analysis of patients who had low complement C3/C4 and who were positive for anti-dsDNA antibodies.

During the course of 1 year, severe disease flares were reduced by 62% among serologically active patients receiving subcutaneous belimumab, 200 mg weekly, compared with those given placebo (HR 0.38, 95% CI 0.24-0.61, P<0.0001), with all patients also receiving standard of care therapy, Andrea Doria, MD, of the University of Padua in Italy, and colleagues reported.

This was a greater reduction than what was seen in the full intent-to-treat population of the initial study (n=839) evaluating the subcutaneous formulation of belimumab (BLISS-SC), in which the reduction in severe flares was 50% compared with placebo (HR 0.50, P=0.0003), they said in a late-breaking presentation at the European Congress of Rheumatology.

Belimumab is a monoclonal antibody that targets B-lymphocyte stimulator (BLyS). It was approved in 2011 as an intravenous treatment for active, autoantibody-positive lupus based on the results of the two phase III BLISS trials.

"Post-hoc analyses of those trials demonstrated that patients with SLE who had low C3/C4 and were positive for anti-dsDNA antibodies, and were therefore considered serologically active, had a greater response to intravenous belimumab than patients without these characteristics," Doria said.

Therefore, to see if this subgroup of patients also would show a greater response with the subcutaneous formulation of belimumab, he and his colleagues analyzed outcomes for the 356 patients in BLISS-SC with serologically active disease.

Patients in BLISS-SC had SLE Disease Activity Scores SLEDAI of 8 or higher at baseline. Among the serologically active subgroup, the mean age was 35, median disease duration was 5 years, and mean SLEDAI was 11.6. At baseline, two-thirds were taking antimalarials, half were on immunosuppressants, and more than 90% were receiving steroids, with a mean prednisone dosage of 12 mg/day.

A total of 248 were in the belimumab arm of the study, while 108 were in the placebo arm. All received standard of care treatment throughout the year-long trial.

The main endpoint was a SLE Responder Index 4 (SRI4), which required a 4 point decrease in the SLEDAI, an increase of more than 0.3 in the physician's global assessment, and minimal changes on the British Isles Lupus Assessment Group index.

At week 52, SRI4 responses were seen in 64.6% of patients in the active treatment group compared with 47.2% of those in the placebo group (OR 2.23, 95% CI 1.36-3.64, P=0.0014), Doria reported. Each component of the SRI4 was statistically significant, he noted.

However, the time to flare was shorter in patients in the belimumab group than in the placebo group (90 days versus 126.5 days).

More patients given belimumab were able to reduce their steroid dose by more than 25% to 7.5 mg/day or less during weeks 40 to 52 (20.7% vs 11.4%), but this was not statistically significant. The study was underpowered for this endpoint, Doria noted.

The overall incidence of adverse events was 78.2% in the belimumab group and 81.5% in the placebo group. The most common events were headache, reported in 10.5% of the active treatment group and in 9.3% of the placebo group, and nasopharyngitis, in 10.1% and 4.6%, respectively.

Serious adverse events occurred in 13.3% of the belimumab group and in 23.1% of the placebo group. Depression was reported by 4.4% and 2.8%, respectively, with one belimumab patient reporting suicidal ideation. Five deaths occurred (1.2% of the belimumab and 1.9% of the placebo groups).

"Subcutaneous belimumab represents a new opportunity in lupus treatment as a biologic therapy that can be administered at the patient's home," commented Amit Saxena, MD, of NYU Langone Medical Center in New York City, who was not involved in the study.

"Due to the fairly modest overall efficacy data in phase III trials of the intravenous version, belimumab earned a somewhat unfair reputation as a milder treatment agent. However, post-hoc analyses on the intravenous data, now confirmed in this study using the subcutaneous trial cohort, established a greater effect size among a subset of patients with evidence of more active lupus serologies," Saxena told MedPage Today.

"These findings may relate to a greater efficacy of belimumab in patients with disease that presents with a more intense immune response, supporting the biology of this treatment," he said.

The study was funded by GlaxoSmithKline (GSK). Several co-authors are company employees.